Abstract

Background

Platinum-based doublet chemo is the standard first-line therapy for advanced NSCLC without a treatable oncogenic aberration. Pembro (anti–PD-1) is approved in the US and EU for previously treated, PD-L1–expressing advanced NSCLC. KEYNOTE-024 (NCT02142738) is an open-label, phase 3 study of pembro vs platinum-doublet chemo as first-line therapy for advanced NSCLC of PD-L1 TPS ≥50% without treatable EGFR mutations or ALK translocations.

Methods

Patients (pts) were randomized to 35 cycles of pembro 200 mg Q3W or 4-6 cycles of investigator's choice of carboplatin or cisplatin + pemetrexed, carboplatin or cisplatin + gemcitabine, or carboplatin + paclitaxel, with optional pemetrexed maintenance for nonsquamous NSCLC. Pts in the chemo arm could crossover to pembro upon PD. Response was assessed every 9 wk (RECIST v1.1, central imaging vendor). Primary end point was PFS. Secondary end points were OS, ORR, and safety. Differences in PFS and OS were assessed in the ITT population using the stratified log-rank test. At the prespecified second interim analysis (data cutoff, May 9, 2016), the study had 97% power to detect a HR of 0.55 for PFS at a 1-sided α = 2.0%.

Conclusions

Pembro demonstrated superior PFS and OS over platinum-based chemo in pts with advanced NSCLC of PD-L1 TPS ≥50%. Along with the lower rate of treatment-related AEs, these data suggest pembro may be the new standard of care for first-line therapy of PD-L1–expressing advanced NSCLC without treatable oncogenic aberrations.

Clinical trial identification

ClinicalTrials.gov number NCT02142738, originally posted May 16, 2014; EudraCT number 2014-000323-25, originally issued 27-Mar-2014